About 50% of the Philadelphia-positive acute leukemias undergo molecular rearrangements outside the now classical bcr sequence (or M-BCR-1) rearranged in chronic myeloid leukemia (CML). Most of the breakpoints on chromosome 22 have been shown to be clustered in a 10.8-kb region of the first intron of the BCR gene (called bcr2 or m-BCR-1). In this report we examined two cases of Ph1 acute lymphoblastic leukemia in adult patients that exhibited breakpoints in a 5-kb segment of the BCR gene first intron, 16 kb upstream of the previously described cluster, suggesting the possibility of a second minor breakpoint cluster. In addition, the breakpoints on chromosome 9 were located in a region just 5' of the c-abl exon la.